Quantification of respiratory parameters in patients with temporal lobe epilepsy

Dysfunction affecting cardiac or pulmonary systems has been postulated as a major factor in sudden death in epilepsy (SUDEP). Whilst the majority of studies of cardiorespiratory function have focused on changes during seizures, here we investigate whether epilepsy influences basal respiratory parameters in patients with temporal lobe epilepsy (TLE) during the interictal period. Spirometry was performed in 10 females and 10 males. Measurements of Vital Capacity (VC), Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second (FEV1) and ratios of FEV1 to FVC (FEV1/FVC) were obtained, and these values were analyzed as percentages of predicted values. None of the patients had chronic obstructive pulmonary disease and no significant alterations in respiratory function tests were found among these patients. No association between seizure frequency, antiepileptic drugs and SUDEP could be found in this study. Although the study did not identify any specific respiratory abnormality in TLE patients during the interictal period, re-evaluation of clinical data on pulmonary disorders in people with epilepsy should be better investigated

Consumo de peixe, contaminantes e morte súbita em epilepsia: mais benefícios do que riscos

People with epilepsy have an increased risk of dying prematurely and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). SUDEP is mainly a problem for patients with chronic uncontrolled epilepsy. The ultimate goal of research in SUDEP is to develop new methods to prevent it and actions other than medical and surgical therapies that could be very useful. Nutritional aspects, i.e., omega-3 fatty acids deficiency, could have an interesting role in this scenario. Some animal and clinical studies have suggested that omega-3 fatty acids could be useful in the prevention and treatment of epilepsy and hence SUDEP. It has been ascertained that the only foods that provide large amounts of omega-3 are seafood (fish and shellfish); however, some fish are contaminated with methylmercury, which may counteract the positive effects of omega-3 fatty acids. Our update review summarises the knowledge of the role of fish consumption on epilepsy research.Pessoas com epilepsia têm um risco aumentado de morrer de forma prematura e a causa mais comum de morte relacionada à epilepsia encontra-se na categoria de morte súbita inesperada em epilepsia (SUDEP). SUDEP é um problema significativo para pacientes com epilepsia crônica não controlada. O principal objetivo nas pesquisas em SUDEP é o desenvolvimento de métodos capazes de levar à sua prevenção e ações outras que não medicamentosas e cirúrgicas que podem ser úteis. Os aspectos nutricionais, como por exemplo, a deficiência do ácido graxo ômega-3 pode ter um papel interessante neste cenário. Alguns estudos animais e clínicos têm sugerido que os ácidos graxos ômega-3 podem ser úteis na prevenção e no tratamento da epilepsia e, consequentemente, na SUDEP. Os únicos alimentos que contêm grandes proporções de ômega-3 são os frutos do mar (peixes e mariscos). No entanto, alguns peixes podem estar contaminados com metilmercúrio, o que pode levar a um efeito contrário ao benefício trazido pelos ácidos graxos ômega-3. Aqui, resumimos o conhecimento do papel do consumo de peixe nas pesquisas em epilepsia.FAPESPCInAPCe-FAPESPCNP

Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex

Mucopolysaccharidosis type I (MPS I) is caused by genetic deficiency of alpha-l-iduronidase and impairment of lysosomal catabolism of heparan sulfate and dermatan sulfate. In the brain, these substrates accumulate in the lysosomes of neurons and glial cells, leading to neuroinflammation and neurodegeneration. Their storage also affects lysosomal homeostasis-inducing activity of several lysosomal proteases including cathepsin B (CATB). In the central nervous system, increased CATB activity has been associated with the deposition of amyloid plaques due to an alternative pro-amyloidogenic processing of the amyloid precursor protein (APP), suggesting a potential role of this enzyme in the neuropathology of MPS I. In this study, we report elevated levels of protein expression and activity of CATB in cortex tissues of 6-month-old MPS I (Idua -/- mice. Besides, increased CATB leakage from lysosomes to the cytoplasm of Idua -/- cortical pyramidal neurons was indicative of damaged lysosomal membranes. The increased CATB activity coincided with an elevated level of the 16-kDa C-terminal APP fragment, which together with unchanged levels of beta-secretase 1 was suggestive for the role of this enzyme in the amyloidogenic APP processing. Neuronal accumulation of Thioflavin-S-positive misfolded protein aggregates and drastically increased levels of neuroinflammatory glial fibrillary acidic protein (GFAP)-positive astrocytes and CD11b-positive activated microglia were observed in Idua -/- cortex by confocal fluorescent microscopy. Together, our results point to the existence of a novel CATB-associated alternative amyloidogenic pathway in MPS I brain induced by lysosomal storage and potentially leading to neurodegeneration

Coupling of vinculin to F-actin demands Syndecan-4 proteoglycan

Syndecans are heparan sulfate proteoglycans characterized as transmembrane receptors that act cooperatively with the cell surface and extracellular matrix proteins. Syn4 knockdown was performed in orderto address its role in endothelial cells (EC) behavior. Normal EC and shRNA-Syn4-EC cells were studied comparatively using complementary confocal, super-resolution and non-linear microscopic techniques. Confocal and super-resolution microscopy revealed that Syn4 knockdown alters the level and arrangement of essential proteins for focal adhesion, evidenced by the decoupling of vinculin from F-actin filaments. Furthermore, Syn4 knockdown alters the actin network leading to filopodial protrusions connected by VE-cadherin rich junction. shRNA-Syn4-EC showed reduced adhesion and increased migration. Also, Syn4 silencing alters cell cycle as well as cell proliferation. Moreover, the ability of EC to form tube-like structures in matrigel is reduced when Syn4 is silenced. Together, the results suggest a mechanism in which Syndecan-4 acts as a central mediator that bridges fibronectin, integrin and intracellular components (actin and vinculin) and once silenced, the cytoskeleton protein network is disrupted. Ultimately, the results highlight Syn4 relevance for balanced cell behavior. (C) 2016 Elsevier B.V. All rights reserved.CAPES (Coordenagdo de Aperfeicoamento de Pessoal de Nivel Superior)CNPq (Conselho Nacional de Desenvolvimento Cientffico e Tecnologico)FAPESP (Fundacao de Amparo a Pesquisa do Estado de sao Paulo), BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Bioquim, Disciplina Biol Mol, Sao Paulo, SP, BrazilUniv Liverpool, Inst Integrat Biol, Dept Biochem, Liverpool, Merseyside, EnglandUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, BrazilUniv Houston, Coll Optometry, TOSI, Houston, TX USAUniv Fed Sao Paulo, Grp Interdisciplinar Ciencias Exatas Saude, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Bioquim, Disciplina Biol Mol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, BrazilUniv Fed Sao Paulo, Grp Interdisciplinar Ciencias Exatas Saude, Sao Paulo, SP, BrazilFAPESP: 15/08782-3FAPESP: 15/03964-6Web of Scienc

Does Pilocarpine-Induced Epilepsy in Adult Rats Require Status epilepticus?

Pilocarpine-induced seizures in rats provide a widely animal model of temporal lobe epilepsy. Some evidences reported in the literature suggest that at least 1 h of status epilepticus (SE) is required to produce subsequent chronic phase, due to the SE-related acute neuronal damage. However, recent data seems to indicate that neuro-inflammation plays a crucial role in epileptogenesis, modulating secondarily a neuronal insult. For this reason, we decided to test the following hypotheses: a) whether pilocarpine-injected rats that did not develop SE can exhibit long-term chronic spontaneous recurrent seizures (SRS) and b) whether acute neurodegeneration is mandatory to obtain chronic epilepsy. Therefore, we compared animals injected with the same dose of pilocarpine that developed or did not SE, and saline treated rats. We used telemetric acquisition of EEG as long-term monitoring system to evaluate the occurrence of seizures in non-SE pilocarpineinjected animals. Furthermore, histology and MRI analysis were applied in order to detect neuronal injury and neuropathological signs. Our observations indicate that non-SE rats exhibit SRS almost 8 (+/22) months after pilocarpine-injection, independently to the absence of initial acute neuronal injury. This is the first time reported that pilocarpine injected rats without developing SE, can experience SRS after a long latency period resembling human pathology. Thus, we strongly emphasize the important meaning of including these animals to model human epileptogenesis in pilocarpine induced epilepsy

19F labelled glycosaminoglycan probes for solution NMR and non-linear (CARS) microscopy

Studying polysaccharide-protein interactions under physiological conditions by conventional techniques is challenging. Ideally, macromolecules could be followed by both in vitro spectroscopy experiments as well as in tissues using microscopy, to enable a proper comparison of results over these different scales but, often, this is not feasible. The cell surface and extracellular matrix polysaccharides, glycosaminoglycans (GAGs) lack groups that can be detected selectively in the biological milieu. The introduction of 19F labels into GAG polysaccharides is explored and the interaction of a labelled GAG with the heparin-binding protein, antithrombin, employing 19F NMR spectroscopy is followed. Furthermore, the ability of 19F labelled GAGs to be imaged using CARS microscopy is demonstrated. 19F labelled GAGs enable both 19F NMR protein-GAG binding studies in solution at the molecular level and non-linear microscopy at a microscopic scale to be conducted on the same material, essentially free of background signals

The il1β have a protective action in the acute phase of the pilocarpine-induced epilepsy model

INTRODUCTION: There is contradictory information regarding the of effects il1β and il1rn in epilepsy. We aimed to evaluate the effect of silencing both genes in the acute phase of the pilocarpine-induced epilepsy model. METHODS: We used RNA interference in order to achieve gene silencing. RESULTS: We obtained significant gene silencing in the central nervous system. In addition, we observed phenotypic effects including differences in mortality rates of animals 5 days after pilocarpine injections. CONCLUSION: Our results indicate that il1β seems to have a protective effect in the acute phase of the pilocarpine-induced epilepsy model.INTRODUÇÃO: Existem contradições na literatura quanto aos efeitos dos genes il1β e il1rn nas epilepsias. Nosso objetivo foi avaliar os efeitos do silenciamento desses dois genes na fase aguda do modelo de epilepsia induzido pela pilocarpina. MÉTODOS: Para alterar a expressão dos genes il1β e il1rn utilizamos a técnica de interferência por RNA. RESULTADOS: Obtivemos taxas de silenciamento significativas para os dois genes no sistema nervoso central. Observamos efeitos fenotípicos significativos, incluindo a alteração na taxa de mortalidade dos animais 5 dias após a indução do modelo. CONCLUSÕES: A il1β parece exercer um papel protetor na fase aguda do modelo de epilepsia induzido pela pilocarpina.979